Abstract:[Background] Marine microorganisms are important source of pharmaceutical active leading compounds and chemical induction can be used as a convenient approach to mine their secondary metabolic potential. [Objective] Based on a marine-derived fungus Aspergillus terreus C23-3, this study aimed to optimize fermentation conditions for more abundant metabolites (including butyrolactones), and exploit the potential of the strains in drugs targeting Alzheimer’s disease. [Methods] The strain was first cultivated on micro-scale, by taking four basic cultures mediums including seawater potato medium, malt extract medium, rice medium and soybean medium, and adopting six chemical inducers including sodium butyrate, suberoylanilide hydroxamic acid (SAHA), 5-azacytidine (5-azaC), procaine hydrochloride, ZnCl2 and CuCl2. The morphological variation of the mycelia was observed. Then, based on the thin layer chromatography (TLC) fingerprints, chemical coloration and bioautography results, inducing conditions with rich new metabolites and rich anti-acetylcholinesterase and antioxidant products were initially screened out for further routine-scale fermentation. Using the above methods and high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis, the diversity of the total metabolites and of butyrolactones was analyzed for the routine fermentation. [Results] The results indicated that CuCl2, ZnCl2, SAHA and 5-azaC caused remarkable changes in the growth morphology of Aspergillus terreus C23-3 mycelium. Six chemical inducing conditions, e.g. seawater potato medium plus 100 μmol/L sodium butyrate, led to diverse bioactive metabolites both in micro-scale cultivation and routine-scale fermentation. Furthermore, its butyrolactone metabolites also displayed difference under different conditions. [Conclusion] Chemical induction approaches can prompt the Aspergillus terreus C23-3 to produce rich bioactive substances, laying foundation for the discovery of diverse anti-Alzheimer’s disease natural products.
